In 15 patients with Bernard-Soulier syndrome from Western India, we amplified the entire coding sequences of GP1BA, GP1BB and GP9 genes and directly sequenced them.
Bernard-Soulier syndrome (BSS) is an extremely rare form of platelet adhesion disorder caused by genetic changes occurring in the glycoprotein genes GPIbα, GPIbβ and GPIX with autosomal recessive inheritance pattern.
A Leu7Pro mutation in the signal peptide of platelet glycoprotein (GP)IX in a case of Bernard-Soulier syndrome abolishes surface expression of the GPIb-V-IX complex.
Transient transfection studies confirmed that mutant GPIX was not expressed on the transfected cells, showing that the mutation was responsible for the BSS phenotype observed in the patient.
Since this mutation is located in the leucine-rich motif (LRM) of the GPIX polypeptide, the Phe55-->Ser substitution may result in an alteration of the LRM which leads to the impaired surface expression of GPIb/IX/V complex, a characteristic of BSS.
We propose that expression of abnormal GPIX prevents stable assembly of the GPIb/IX complex, causing BSS in the doubly heterozygous individuals in this family.